Chapter 3 - Neuroimaging Biomarkers in Alzheimer’s Disease

Abstract

Neuroimaging of the brain holds promise as a noninvasive method to identify preclinical AD and individuals who are at high risk of dementia. Extensively researched neuroimaging biomarkers of AD include brain atrophy, amyloid plaques, hyperphosphorylated tau, glucose hypometabolism, abnormal cerebral blood flow, neuronal activity, and regional brain metabolites. Imaging modalities used to detect these markers include positron emission tomography (PET), magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), electroencephalography (EEG), and single-photon emission computed tomography (SPECT). Thus far, PET biomarkers have been shown to be the best predictors of AD progression. Brain atrophy measured by MRI is now being considered as a valid biomarker of mild cognitive impairment (MCI), and may also be useful for preclinical detection of AD. In this chapter, we critically evaluate neuroimaging biomarkers of AD and discuss their clinical utility for early diagnosis of AD; capacity for longitudinal assessment, detection of AD prodromal stages, and conversion of MCI to AD; use in evaluating therapeutic efficacy in AD clinical trials, and ability to differentiate AD from other neurodegenerative diseases such as frontotemporal dementia (FTP), Lewy body dementia (LBD), vascular dementia (VaD), Creutzfeldt–Jacob disease (CJD), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and tauopathy. This chapter also provides an overview of how neuroimaging biomarkers may be used as surrogate end points in AD clinical trials. Though neuroimaging is a less invasive method for detecting AD biomarkers, it is also expensive and requires highly trained personnel, making it unsuitable for use in the primary care, office-based clinical setting. More widespread adoption of neuroimaging AD biomarkers is also limited by technical challenges to achieving sufficient sensitivity and specificity.